engleski

Perinatal exposure to 5-hydroxytryptamine or tranylcypromine alters structure of the barrel field in rat pups

Serotonin (5-hydroxytryptamine, 5HT) is a bioactive monoamine involved in the regulation of many physiological functions. In the developing brain, 5HT acts as a neurodevelopmental signal regulating outgrowth of its own neurons and maturation of target regions. Growing evidence suggested the role of 5HT signaling in the modulation of pre- and early post-synaptic development of a region in the rodent primary somatosensory cortex called the barrel field. The barrel field contains distinct cytoarchitectonic features called “barrels”, consisting of clustered presynaptic thalamocortical axons (TCA) surrounded by postsynaptic layer IV neurons, separated from each other by cell-free areas (septa). Drugs targeting the 5HT system are widely used in treatments of affective and anxiety disorders, also during pregnancy. Although the consequences of developmental exposure to selective serotonin reuptake inhibitors have been widely studied on animal models, similar data on possible effects of perinatal exposure to 5-hydroxytryptophan, 5HTP (the immediate 5HT precursor sometimes considered as a natural and safer alternative to antidepressant medication) and tranylcypromine, TCP (a monoamine oxidase inhibitor prescribed in patients resistant to other antidepressants) on brain development are seriously lacking. In this study we examined possible developmental disturbances, as reflected in barrel field formation, in rat pups perinatally treated with 5HTP or TCP. Wistar rats were treated with either 25mg/kg of 5HTP, 2mg/kg TCP, or saline, from gestational day 13 until birth by subcutaneous injections to pregnant females, and from postnatal day (PND) 1 until PND 21 by receiving subcutaneous injections themselves. Brain samples were collected on PND 22. Cytoarchitecture of barrel fields was analyzed after Nissl staining of tangentially oriented serial sections across the dorsolateral telencephalic wall. The size of the barrels was measured on scanned slices using NIH ImageJ software. Both treatments altered the formation of the barrel cortex, although in a different manner. While, the barrels of TCP-treated pups seemed diffused with poorly defined walls, barrels of 5HTP-treated animals appeared well-defined, but were significantly smaller in comparison to those of the control rats. Our results obtained on an animal model suggest a need for thorough examination of the potential effects of these two 5HT-enhancers on the developing human brain.

serotonin; perinatal treatment; 5-hydroxytryptophan; tranylcypromine; barrel field; rat

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